Soft tissue mechanical properties indicate organ health and impact tissue function. This is perhaps nowhere more obvious than in the blood, where the transition from a fluid to a solid (coagulation) can preserve life during trauma and end life during heart attack, stroke, and pulmonary embolism. While a failure to coagulate (hemophilia) is easily identified and fairly effectively treated, inappropriate coagulation remains responsible for 35% of all deaths in the U.S.. Diagnosis of coagulation disorders is critical for identifying those at risk and implementing appropriate treatment and prophylaxis. The goal of this proposal is refinement and clinical validation of an ultrasound radiation force based approach for measuring soft tissue mechanical properties. In this proposal we focus on sonorheometry for coagulation assessment, however the proposed developments will support other future applications. By inducing displacements of only a few microns, sonorheometry avoids disrupting clot formation and therefore provides a fundamentally better measure of overall coagulation risk than existing methods. Sonorheometry will be developed, enhanced, and evaluated through the following specific aims: 1. Implement and Optimize Sonorheometry on the Ultrasonix Sonix RP System 2. Utilize Theory, Simulations, and Experiments to Validate Sonorheometry with High Strain Rates 3. Enhance Algorithms to Improve Accuracy and Reduce Processing Time 4. Test the Ability of Sonorheometry to Identify Hypercoagulability among Human Subjects A successful outcome in assessing hypercoagulability could have a large and immediate clinical impact as it would quantify the magnitude of acquired hypercoagulability (such as that from tobacco smoking and oral contraceptive use). Our collaboration with B. Gail Macik, M.D. of the UVA Division of Hematology and Medical Oncology will identify additional applications and ensure that our work remains clinically relevant. [unreadable] [unreadable] [unreadable]